Cutaneous patches, such as transdermal patches, are popular methods of non-invasive controlled release drug delivery. Additional uses of patch technology include appetite stimulation and/or suppression, for weight increase/maintenance or control. Advantages of transdermal delivery include avoidance of gastrointestinal side-effects, avoidance of the hepatic first-pass effect, maintenance of therapeutic drug levels for up to one week, reduction of drug peak-related side effects, improved patient compliance, and easy termination of drug input. Example transdermal drug delivery systems are currently available for nicotine (over the counter formulations by various manufacturers), clonidine (for example, CATAPRES), and fentanyl (for example, DURAGESIC).
Currently available transdermal delivery systems are effective for their intended purposes, but would benefit from improvements. For example, it is known that nicotine replacement smoking cessation therapy is improved by delivering nicotine at a similar rate as would be derived by smoking a cigarette, which results in peaks in plasma nicotine and improved satisfaction of cravings (Benowitz et al., Sources of variability in nicotine and cotinine levels with use of nicotine nasal spray, transdermal nicotine, and cigarette smoking, Brit. J. of Clin. Pharm. (1997) 43, 259-267; Russell, Nicotine replacement: the role of blood nicotine levels, their rate of change, and nicotine tolerance, In: Pomerleau et al., eds., Nicotine replacement: a critical evaluation, New York: Alan R. Liss, 1988, 187-217). However, conventional nicotine patches deliver nicotine at a constant rate resulting in steady plasma nicotine levels, and are therefore less effective (Gourlay et al., Double blind trial of repeated treatment with transdermal nicotine for relapsed smokers, BMJ (1995) 311, 363-6).
As another example, use of clonidine during opiate withdrawal therapy often requires an extremely complex dosing regimen. Current transdermal patch technologies cannot easily be adapted to such dosing regimens, and accordingly oral clonidine therapy is much more common. Delivery of clonidine therapy via a transdermal delivery system capable of providing a complicated, staggered dosage regimen would allow less medical supervision, decreasing health care costs. Still further, a programmable transdermal delivery system would allow flexibility in delivery and withdrawal rates for the drug, allowing flexibility in dose titration during delivery and also during withdrawal from the drug, reducing the rebound effects associated with clonidine withdrawal.
The present invention addresses the identified need in the art by providing a cutaneous delivery system for a composition, comprising an ordered nanoporous membrane and a reservoir in fluid communication with the membrane. The nanoporous membrane of the present invention can be functionalized in a variety of ways at the pore openings to impart selectivity to the membrane, to provide a selectively gateable membrane as well as other functions. A cutaneous delivery device for a composition is provided also. In one embodiment, the cutaneous delivery device is adapted to deliver the composition selectively in response to an electrical impulse.